General Information of Binding Target of SBP (BTS) (ID: ST00007)
BTS Name
Ephrin type-A receptor 2
Synonyms
EC 2.7.10.1; Epithelial cell kinase; Tyrosine-protein kinase receptor ECK
BTS Type
Protein
Family
Protein kinase superfamily;
Tyr protein kinase family;
Ephrin receptor subfamily
Gene Name
EPHA2
Organism
Homo sapiens (Human)
Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.; (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.
UniProt ID
P29317
UniProt Entry
EPHA2_HUMAN
PFam
PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536
Gene ID
1969
Sequence
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMN
DMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFN
LYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYL
AFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGG
EEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPS
PEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDI
VYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSG
LVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSN
SYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGG
VAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQA
VLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDF
LGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGML
RGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIP
IRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPM
DCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSG
SEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAY
SLLGLKDQVNTVGIPI
Sequence Length
976
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Abdurin anti-EphA2/FcRn B11 Research Binder Kd: 4.4 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Abdurin anti-EphA2/FcRn B6 Research Binder Kd: 6.5 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Abdurin anti-EphA2/FcRn D2 Research Binder Kd: 2.6 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Abdurin anti-EphA2/FcRn G7 Research Binder Kd: 8.1 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
Bicyclic peptide anti-EphA2 clone 6044 Research Binder Kd: 2.8 nM Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[2]
Bicyclic peptide anti-EphA2 clone 6065 Research Binder Kd: 5.8 nM Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[2]
Bicyclic peptide anti-EphA2 clone 6088 Research Binder Kd: 2 nM Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[2]
Bicyclic peptide anti-EphA2 clone 6099 Research Binder Kd: 5.7 nM Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[2]
Bicyclic peptide anti-EphA2/CD137 BT7455 Research Binder N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[3]
Bicyclic peptide BT5528 Phase II Inhibitor N.A. Non-small cell lung cancer [ICD-11: 2C25.Y]; Breast cancer [ICD-11: 2C6Z]; Bladder cancer [ICD-11: 2C94.Z]; Esophageal cancer [ICD-11: 2B70.Z]; Gastric cancer [ICD-11: 2B72.Z]; Ovarian cancer [ICD-11: 2C73.Z]
SBP Info
[2], [4]
Monobody anti-EphA2 E1 Research Binder Kd: 1.8 nM Imaging agent for patients with EphA2-expressing tumors
SBP Info
[5], [6]
Monobody anti-EphA2 E10 Research Binder Kd: 2.1 nM Cancers [ICD-11: 2D4Z]
SBP Info
[7]
References
1 High Affinity Binders to EphA2 Isolated from Abdurin Scaffold Libraries; Characterization, Binding and Tumor Targeting. PLoS One. 2015 Aug 27;10(8):e0135278.
2 Identification and Optimization of EphA2-Selective Bicycles for the Delivery of Cytotoxic Payloads. J Med Chem. 2020 Apr 23;63(8):4107-4116.
3 Bicycle therapeutics. Product Development Pipeline. 2021.
4 MMAE Delivery Using the Bicycle Toxin Conjugate BT5528. Mol Cancer Ther. 2020 Jul;19(7):1385-1394.
5 Production of 64 Cu-labeled monobody for imaging of human EphA2-expressing tumors. Bioorg Med Chem Lett. 2020 Jul 15;30(14):127262.
6 Engineering of monobody conjugates for human EphA2-specific optical imaging. PLoS One . 2017 Jul 7;12(7):e0180786.
7 Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2. PLoS One. 2015 Jul 15;10(7):e0132976.